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Biomedical subjects

K Nozaki

Publications and source records attributed to K Nozaki.

At least 19 recordsLinked to original sources

Expression of c-fos-like immunoreactivity in brainstem after meningeal irritation by blood in the subarachnoid space.

The expression of c-fos protein was examined by immunohistochemistry in serial sections of brainstem following the instillation of either autologous arterial blood (0.3 ml) or mock cerebrospinal fluid (0.3 ml) through a catheter placed in the cisterna magna, or following catheter placement alone in pentobarbital-anesthetized Sprague-Dawley rats. After injection, blood was distributed within the subarachnoid space surrounding the brainstem and in the region of the circle of Willis. c-fos protein-like immunoreactivity was present at 1 h, peaked at 2 h and decreased by 8 h. At 2 h, immunoreactivity was strongly expressed within trigeminal nucleus caudalis (lamina I, IIo), as well as within nucleus of the solitary tract, area postrema, ependyma, pia mater and arachnoid in every animal. Moderate labeling was found in parabrachial nucleus, medullary lateral reticular nucleus and central gray. Sparse labeling was present in trigeminal nucleus caudalis (lamina III-V) and trigeminal nucleus interpolaris; few or no labeled cells were detected in other parts of the trigeminal nuclear complex, thalamus, cerebral cortex, cerebellar cortex or trigeminal ganglion. The number of positive cells was not related to the volume of injectate but was related to the amount of injected blood. The density of cell labeling evoked by injecting mock cerebrospinal fluid or after catheter placement was markedly lower than after blood in all brainstem areas. The number of labeled cells was greatly reduced within trigeminal nuclear complex, parabrachial nucleus and medullary lateral reticular nucleus, but not within the nucleus of the solitary tract, area postrema or ependyma when blood was injected into adult animals in which unmyelinated C-fibers were destroyed by neonatal capsaicin treatment. Similar results were obtained after blood was instilled into the cisterna magna of rats in which meningeal afferents were chronically sectioned at the ethmoidal foramen bilaterally. We conclude that blood in the subarachnoid space is an effective stimulus for activating c-fos expression within subpopulations of brainstem neurons. Activation within trigeminal nucleus caudalis is mediated in large part by excitation of small-caliber meningeal afferents (trigeminovascular fibers), whereas c-fos expression within nucleus of the solitary tract and area postrema may reflect direct stimulation of blood or blood products, or possibly the response to autonomic activation from noxious stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Ring 14 chromosome with complex partial seizures: a case report.

A two-year-old girl was found to have a ring 14 chromosome: [46, XX, r(14) (P13 q32.3)]. Her development, including verbal ability, was retarded, her CT scan displayed a low density area anterior to the left temporal lobe, and she suffered from complex partial seizures. Focal central nervous system abnormalities may be present in patients with ring 14 chromosome, and their seizures are not exclusively of the primary generalized type. This is the first case with ring 14 chromosome and complex partial seizures.

Child

Neuroprotective effects of L-kynurenine on hypoxia-ischemia and NMDA lesions in neonatal rats.

Kynurenic acid is the only known endogenous excitatory amino acid receptor antagonist in the central nervous system. In the present study, we examined whether increasing brain concentrations of kynurenic acid by loading with its precursor L-kynurenine, or blocking its excretion with probenecid, could exert neuroprotective effects. Neuroprotective effects were examined in a neonatal model of hypoxia-ischemia, and following intrastriatal injection of N-methyl-D-aspartate (NMDA). Seven-day-old rats underwent unilateral ligation of the carotid artery, followed by exposure to 8% oxygen for 1.5 h. L-kynurenine administered 1 h before the hypoxia-ischemia showed a dose-dependent significant neuroprotective effect, with complete protection at a dose of 300 mg kg-1. The induction of c-fos immunoreactivity in cerebral cortex was also blocked by this dose of L-kynurenine. Probenecid alone had moderate neuroprotective effects, while a combination of a low dose of probenecid with doses of 50-200 mg kg-1 of L-kynurenine showed significant dose-dependent neuroprotection. Kynurenine dose-dependently protected against NMDA neurotoxicity in 7-day-old rats. Neurochemical analysis confirmed that L-kynurenine with or without probenecid markedly increased concentrations of kynurenic acid in cerebral cortex of 7-day-old rats. These results show for the first time that pharmacologic manipulation of endogenous concentrations of kynurenic acid can exert neuroprotective effects.

Animals

CP-93,129, sumatriptan, dihydroergotamine block c-fos expression within rat trigeminal nucleus caudalis caused by chemical stimulation of the meninges.

1. The effects of intravenously administered 5-HT1B receptor agonists were examined on c-fos like immunoreactivity, an indicator of neuronal activation, within the brain stem. C-fos was induced by injecting an algesic, vasoconstrictor substance (0.3 ml of autologous blood) or a pro-inflammatory molecule, carrageenin (1 mg in 0.1 ml saline) into the cisterna magna of pentobarbitone-anaesthetized Sprague-Dawley rats and was visualized in serial sections (50 micrometers) by use of a polyclonal antiserum. 2. As previously reported, the injection of blood caused significant labelling within laminae I, IIo of the trigeminal nucleus caudalis, a major nociceptive brain stem nucleus, as well as within nucleus of the solitary tract and area postrema. A similar pattern of expression with fewer cells per section was detected after carrageenin instillation. The number of expressing cells was reduced by 54% in trigeminal nucleus caudalis but not within the nucleus of the solitary tract or area postrema when blood was injected in adult rats neonatal capsaicin treatment. 3. Pretreatment with 5-HT1 agonists with some selectivity for the 5-HT1B receptor, CP-93,129 (460 nmol kg-1 x 2, i.v.), sumatriptan (720 nmol kg-1 x 2, i.v.) or dihydroergotamine (86 nmol kg-1 x 2, i.v.) reduced positive cells by 39%, 31%, and 33% respectively in trigeminal nucleus caudalis but not in nucleus of the solitary tract or area postrema after blood instillation. Pretreatment with the analgesic morphine (15 mumol kg-1, s.c.) also decreased the number of positive cells by 63% in trigeminal nucleus caudalis. 4. CP-93,129 (460 nmol kg-1 x 2, i.v.) reduced the number of c-fos labelled cells by 47% within lamina I, IIo after carrageenin instillation. 5. Drug-induced blockade appeared to be tissue-dependent. Pretreatment with sumatriptan (720 nmol kg-1 x 2, i.v.) did not block c-fos expression in trigeminal nucleus caudalis following formalin application to the nasal mucosa.6. Drug-induced blockade may be mediated by an action on primary afferent (trigeminovascular) fibres in as much as CP-93,129 (460 nmol kg-' x 2, i.v.) did not reduce the number of expressing cells within the trigeminal nucleus caudalis following blood instillation in rats treated as neonates with capsaicin.7. We infer from these results that the analgesic actions of agonists at 5-HTB receptors (the receptor subtype analogous to 5-HTID in man) need not depend upon the presence of vasodilatation and, that 5-HTID receptor-mediated blockade of neurotransmission contributes significantly to the analgesic effects of these drugs in headache.8. Based on the demonstrated effects of 5-HTB/D agonists against the actions of two chemicallyunrelated meningeal stimulants, we suggest that treatment with 5-HTID agonists may be useful for the alleviation of pain in other headache conditions associated with meningeal irritation. Bacterial, viral(including AIDS meningovascular inflammation) and other forms of chemical meningitis merit further investigation.

Animals

Preventive effect of synthetic serine protease inhibitor, FUT-175, on cerebral vasospasm in rabbits.

The effect of the synthetic multiserine protease inhibitor FUT-175 on cerebral vasospasm after subarachnoid hemorrhage (SAH) was investigated in rabbits. The SAH in rabbits was simulated by a single injection of autologous arterial blood into the cisterna magna, and, for 7 days, the caliber of each basilar artery was examined several times via angiogram. In 10 SAH rabbits, the peak of the arterial narrowing was observed on Day 2. In this model, the effect of intravenous administrations of FUT-175 was examined. Twenty-seven SAH rabbits were randomly divided into three groups, and 3 doses of 1, 2, or 3 mg of FUT-175 were administered intravenously. Angiographic arterial narrowing on Day 2 in nontreated SAH rabbits (Control) was 35% compared with 21, 5, and 14% in rabbits treated with a total of 3 (Group A; n = 9), 6 (Group B; n = 13), and 9 mg (Group C; n = 5) of FUT-175, respectively. There were statistically significant differences in the arterial calibers between Group A and the Control on Days 1 and 2, between Group B and the Control from days 1 to 4, and between Group C and the Control from days 1 to 4. In three other rabbits, after vasospasm reached its maximum on Day 2, no vasodilatory effect was observed when a total of 6 mg of FUT-175 was administered intravenously. The results indicate that the inhibition of the plasma serine protease cascades at an early stage of SAH prevents the development of cerebral vasospasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effects of pulsing electromagnetic fields on the ligament healing in rabbits.

Effects of pulsing electromagnetic fields (PEMFs) on ligament healing were investigated using 80 rabbits. All animals received square resection (4 mm x 4 mm) of both patellar ligaments in full thickness at their center. They were divided into 4 groups of 20 rabbits each and stimulated with different electromagnetic intensity of 0 (control), 2, 10, and 50 gauss (G) for 6 hr daily. Pulse frequency and pulse width were 10 Hz and 25 microseconds, respectively. After PEMFs stimulations for 1, 2, 3 and 4 weeks, 5 animals of each group were euthanized and the regenerated tissue at the defective portion was investigated histologically and biomechanically. Histologically, the tissue stimulated by PEMFs showed an earlier increase in capillaries and fibroblasts and more matured, prominent longitudinal orientation of collagen fibers than those of control groups. Among the rabbits stimulated electromagnetically, those stimulated at 50 G revealed the earliest ligament healing. Tensile strength of regenerated ligament tissues of any PEMFs groups increased significantly at 1 and 2 weeks after operation, however, at 3 and 4 weeks after operation, there were no significant differences between groups. Among these values, those of 50 G group were the highest consistently during most of the experimental period. From the above results, PEMFs enhanced the earlier stage of ligament healings and 50 G gauss seemed to be the most effective among the 3 field intensities used. This promoting effect may potentiate the earlier recovery of the function after the ligament injury.

Animals

Recurrent intracranial germinoma refractory to conventional irradiation: effective chemotherapy consisting of cisplatin and etoposide--case report.

Recurrent intracranial germinoma with multiple spinal metastases occurred in a 16-year-old male presenting with persistent headache and visual disturbances. Computed tomography revealed enhanced lesions in the pineal region, anterior horn, and infundibulum. Conventional irradiation achieved remission, but local recurrences requiring further irradiation occurred after 23 months. Magnetic resonance imaging showed multiple spinal metastases 11 months later. Partial removal of the spinal lesions gave a histological diagnosis of typical germinoma. Postoperatively, intracranial recurrences were again detected. Chemotherapy consisting of intravenous cisplatin and etoposide achieved remission and no recurrence has occurred for 12 months.

Adolescent

A human skeleton from the Ohguruwa remains.

In 1941, the Ohguruwa remains were discovered at the Mizuho sports ground site in Nagoya. They date from about 3000 B.C., which is the early Jomon era. When the stadium was reconstructed in 1980, four human skeletons were found. Three of them, however, were in poor condition and moreover, were incomplete. However, the second skeleton was in good condition and could almost be reconstructed, and this skeleton (No. 2) was used for our study. It was found in the classic posture with arms and legs folded. Some pieces of a dog's skeleton were also discovered near the No. 2 skeleton's chest. This particular skeleton generally showed characteristics typical of the Jomon era. It had a stout structure and was judged to be a middle aged male because of the following features. There was considerable attrition of the occlusal surfaces on the remaining teeth. The teeth were worn flat, probably owing to the hard food and to their use as a tool. Both canines and first premolars of the upper and lower arches had been extracted in accordance with the custom of the time. Typical caries and localized periodontal breakdown were not observed, although there was horizontal alveolar bone loss, especially in the anterior regions. The mastoid process was extremely large and prominent. The lateral prominence of the mandible was developed. Analysis of lateral cephalogram revealed that the mandible was in the anterior position. The angles of SNA, SNB and ANB were 89.6 degrees, 89.2 degrees and 0.4 degrees, respectively. The skeletal pattern was definitive Class III. The adaptive changes in the teeth, their supporting tissues, temporomandibular joints and the related muscles--the harmonious masticatory system--were all estimated.

Cephalometry

Origins and distribution of cerebrovascular nerve fibers showing calcitonin gene-related peptide-like immunoreactivity in the major cerebral artery of the dog.

The origins and overall distribution of perivascular nerve fibers showing calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) in the major cerebral arteries were investigated immunohistochemically in the dog by using whole-mount preparations of the arterial trees around the circle of Willis. Perivascular nerve fibers with CGRP-LI were seen most abundantly in the basilar artery, vertebral artery, common anterior cerebral artery, proximal part of the anterior cerebral artery, and terminal part of the internal carotid artery. They were far less numerous in the middle cerebral artery, posterior cerebral artery, superior cerebellar artery, and distal part of the anterior cerebral artery. Neuronal cell bodies with CGRP-LI were observed in the trigeminal, nodose, superior cervical, and dorsal root ganglia. CGRP-LI fibers in the large pial arteries in the circle of Willis were eliminated ipsilaterally after unilateral transection of the ophthalmic division of the trigeminal nerve, and slightly reduced in number ipsilaterally after unilateral transection of the maxillary division of the trigeminal nerve. They did not show any noticeable changes after unilateral transection of the mandibular division of the trigeminal nerve. On the other hand, CGRP-LI fibers in the basilar and vertebral arteries did not show any appreciable changes after unilateral transection of the trigeminal nerve, but they were eliminated after bilateral ganglionectomy of the dorsal root ganglia of the first, second, and third cervical nerves. After ganglionectomy of the ciliary, pterygopalatine, otic, nodose, or superior cervical ganglion, no changes were observed in perivascular nerve fibers with CGRP-LI in the major cerebral arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Erythrocytes suppress calcitonin gene-related peptide- and vasoactive intestinal polypeptide-like immunoreactivities in cerebrovascular nerve fibers after subarachnoid hemorrhage.

Changes of calcitonin gene related-peptide (CGRP)- and vasoactive intestinal polypeptide (VIP)-like immunoreactivities (LI) in cerebrovascular nerve fibers on the dog basilar artery were immunohistochemically examined by using whole-mount preparations after single percutaneous injection of blood components into the cisterna magna. Blood components were prepared from autologous arterial blood. CGRP- and VIP-LI in cerebrovascular nerve fibers were highly suppressed after the injection of washed erythrocytes, but only moderately after the injection of platelet-rich or platelet-poor plasma. The results suggest that erythrocytes may suppress CGRP- and VIP-LI in cerebrovascular nerve fibers after subarachnoid hemorrhage.

Animals

[Reversal of experimental cerebral vasospasm by neuropeptides].

Changes in the density of cerebroarterial nerve fibers containing calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP)-like substance, as well as changes in dilatory responses of isolated cerebral arteries to these neuropeptides, after subarachnoid hemorrhage (SAH) were examined in dogs. Moreover, the effects of these neuropeptides to the experimentally produced cerebral arterial spasm were also examined in dogs. SAH was produced by a single injection of fresh autologous arterial blood (1 ml/kg body weight) or double injection of arterial blood (0.5 ml/kg body weight, 48 hours apart) into the cisterna magna. Constriction of basilar artery was most prominent on Day 3 in the single injection model, and on Day 7 in the double injection model. The density of nerve fibers with CGRP-or VIP-like immunoreactivity (LI) was markedly decreased during 7-14 days or 3-7 days after SAH. Vasodilatory actions of CGRP and VIP to isolated basilar artery in vitro were markedly impaired during acute stage of post-SAH period and significantly enhanced during chronic stage of post-SAH period. Intracisternal bolus injection of 10(-10) mol/kg CGRP completely reversed cerebral arterial constriction on Day 3 of single injection SAH model, and intracisternal injection of 10(-11) to 2 x 10(-10) mol/kg CGRP reversed cerebral vasospasm dose-dependently. Intraarterial injection of CGRP could not reversed cerebral arterial constriction. The effects of VIP was much weaker than CGRP.

Animals

Changes of glycogen and ATP contents of the major cerebral arteries after experimentally produced subarachnoid haemorrhage in the dog.

The contents of glycogen and ATP in the major cerebral arteries were examined in dogs undergoing subarachnoid haemorrhage (SAH). SAH was produced by a single injection of autologous arterial blood (1 ml/kg body weight) into the cisterna magna. Vertebral angiograms showed biphasic basilar arterial narrowings after the injection of blood: Early arterial narrowing occurred immediately after the injection and continued for a few hours. Late arterial narrowing occurred from Day 1 to Day 14 of post-SAH period, and recovered to the normal level on Day 21 of post-SAH period. The content of glycogen in the large pial arteries significantly decreased from Day 1 to Day 14 and returned to the control level on Day 21. The content of ATP in the large pial arteries also decreased from Day 1 to Day 7 and returned to the control level on Day 14. These results show that energy stores in the major cerebral arteries might be diminished during late arterial narrowing.

Adenosine Triphosphate

Red blood cells are essential for late vasospasm following experimentally induced subarachnoid hemorrhage in dogs.

The in vivo spasmogenic activity of various blood components was examined in dogs. Each blood fraction was injected into the cisterna magna at 0.5 or 1.0 ml/kg body weight, after the removal of 0.5 ml/kg body weight of cerebrospinal fluid, and vertebral angiography was then performed. Whole blood induced both early and late arterial spasm. Platelet-rich and platelet-poor plasma produced only early spasm, and no arterial narrowing was observed on days 1, 3, and 7 after injection. On the contrary, intracisternal injection of washed red blood cells (0.5 ml/kg body weight) produced no arterial narrowing for 6 hours after injection and induced moderate arterial narrowing on days 1, 3, and 7 after injection. Hemolysate (a 10-gm/dl concentration of hemoglobin) produced prolonged monophasic arterial narrowing after injection. These results imply that red blood cells are required for late, prolonged arterial narrowing after experimental subarachnoid hemorrhage.

Animals

Vascular relaxation properties of calcitonin gene-related peptide and vasoactive intestinal polypeptide in subarachnoid hemorrhage.

The vascular relaxation effects of calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) on the dog basilar artery after experimentally produced subarachnoid hemorrhage (SAH) were examined in vitro by an isometric tension recording method. Both CGRP and VIP induced dose-dependent relaxations in ring segments of the intact basilar artery of control dogs. The vasorelaxant action of CGRP was more potent than that of VIP. The single-injection model of SAH was produced by injection of fresh autologous arterial blood (1 ml/kg body weight) into the cisterna magna on Day 0 of the post-SAH period, and the double-injection model was produced by two injections of blood (0.5 ml/kg each) on Days 0 and 2. Narrowing of the basilar arteries on vertebral angiograms was most prominent on Day 3 or 7 in the single- or double-injection model, respectively. Relaxation of the basilar artery induced by CGRP and VIP was to some extent decreased on Days 3 and 7 of the post-SAH period in the single-injection model, and on Days 7 and 14 in the double-injection model. However, the vasorelaxant effects of CGRP and VIP were significantly enhanced on Day 14 of the post-SAH period in the single-injection model, and on Days 28 and 42 in the double-injection model. Subsequently, these effects returned to control levels by Days 28 or 63 in the single- or double-injection model, respectively.

Animals

Changes of calcitonin gene-related peptide-like immunoreactivity in cerebrovascular nerve fibers in the dog after experimentally produced subarachnoid hemorrhage.

After producing a model of subarachnoid hemorrhage (SAH) by a single injection of fresh autologous arterial blood into the cisterna magna in the dog, we immunohistochemically examined changes of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) in perivascular nerve fibers in the large pial arteries by using whole mount preparations. CGRP-LI in cerebrovascular nerve fibers was suppressed after SAH. The suppression was first detected on the 3rd day after SAH, and was most marked during the 7th to 14th day after SAH. CGRP-LI, however, recovered to a normal level by the 42nd day after SAH.

Animals

Electron microscopic studies of viruses labeled with magnetite.

We were able to develop a method with which to successfully and specifically detect virus particles under the electron microscope by using magnetite. This method was devised on the principle that magnetite-labeled antibody or magnetite coupled with protein A selectively bind virus or antibody-treated virus particles on the electron microscope grid by the action of an electromagnet. Another advantage characterizing the technique is the possibility of detection of a small number of virus particles. This is done through a process of concentration and purification of the reaction complexes trapped rigidly by magnetic force.

Antibodies, Viral

Relaxant effect of calcitonin gene-related peptide on cerebral arterial spasm induced by experimental subarachnoid hemorrhage in dogs.

This study examines the relaxant effect of calcitonin gene-related peptide (CGRP), a 37-amino acid peptide with a potent vasodilator action, on cerebral arterial spasm after subarachnoid hemorrhage (SAH). The spasm was induced by injecting autologous arterial blood percutaneously into the cisterna magna in adult mongrel dogs. The single-injection model of SAH was produced by injection of 1.0 ml/kg body weight of blood (on Day 0), and the double-injection model involved two successive injections of 0.5 ml/kg body weight of blood made 48 hours apart (on Day 0 and Day 2). On vertebral angiograms, arterial narrowing of the major cerebral arteries was most prominent on Day 3 after SAH in the single-injection model and on Day 7 in the double-injection model. When 10(-10) mol/kg of CGRP was administered intracisternally in the single-injection model on Day 3, the diameter of the spastic cerebral arteries, as determined by angiography, recovered to normal. After intracisternal administration of 10(-11) to 2 X 10(-10) mol/kg of CGRP on Day 7 in double-injection models, spastic cerebral arteries dilated in a dose-dependent manner. The dilatory effect of CGRP continued for a few hours after administration. The results suggest that CGRP injected intracisternally may reverse cerebral arterial spasm after SAH.

Animals